Thiazolylcinnamonitriles and pest controlling agents

ABSTRACT

Compounds represented by the general formula (1); and pest controlling agents containing one or more of the compounds as the active ingredients, wherein A is substituted phenyl, C 1 -C 6  alkly or the like; B is hydrogen, optionally substituted phenyl or the like; R is C 1 -C 6  alkly, a group represented by the general formula: COR 1  (wherein R 1  is C 1 -C 12  alkyl, C 1 -C 6  alkoxy, C 1 -C 6  haloalkyl or the like) or the like; X is halogeno, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl or the like; and n is an integer of 1 to 5.

FIELD OF INVENTION

The present invention relates to novel thiazolylcinnamonitriles and pest controlling agents containing the said compounds as active ingredients.

BACKGROUND ART

A large number of pest controlling agents, such as insecticides and acaricides, have been used so far. However, many of them are hardly satisfactory as controlling agents because of insufficient efficacy, restrictions on their use due to drug resistance problems, phytotoxicity or pollution on plants, or strong toxicity on humans, domestic animals and fish. Therefore, there has been a desire for the development of agents applicable safely and having less of the drawbacks mentioned above.

As for cinnamonitrile derivatives similar to the compounds of the present invention, for example, 3-hydroxy-2-(4-phenyl-2-thiazolyl)-cinnamonitriles are disclosed in Japanese Patent Laid-open No. Sho 53-92769, Japanese Patent Laid-open No. Sho 55-154963 and EP 189960, and their alkali metal and ammonium salts in Japanese Patent Laid-open No. Sho 55-154962. However, none of them has been put to practical use as insecticides because of insufficient efficacy and other problems.

Further, WO 95/29591 and Japanese Patent Laid-open No. Hei 10-158254 have disclosed cinnamonitrile derivatives, similar to the compounds of the present invention, that are useful as anti-fouling agents for aquatic adhesive organisms. There are, however, no descriptions on their insecticidal activities.

DISCLOSURE OF THE INVENTION

It is an object of the present invention to provide pest controlling agents containing thiazolylcinnamonitriles as active ingredients, that have sure efficacy and can be used safely.

The present invention is directed to compounds represented by Formula (1)

[wherein

A is halogen, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy, optionally substituted C₃₋₆ cycloalkyl, optionally substituted pyridyl, optionally substituted thienyl, substituted phenyl or optionally substituted phenoxy;

B is hydrogen, halogen, C₁₋₆ alkoxycarbonyl, optionally substituted phenyl, C₁₋₆ alkyl, C₁₋₆ haloalkyl or C₃₋₆ cycloalkyl;

R is C₁₋₆ alkyl, a group of Formula COR¹ (wherein R¹ is C₁₋₁₂ alkyl, C₁₋₆ haloalkyl, optionally substituted C₃₋₆ cycloalkyl, C₁₋₆ alkoxy, C₁₋₆ alkoxy C₁₋₆ alkyl, C₁₋₆ alkylthio C₁₋₆ alkyl, mono-C₁₋₆ alkylamino, di-C₁₋₆ alkylamino, optionally substituted phenyl C₁₋₆ alkyl, optionally substituted phenoxy C₁₋₆ alkyl, optionally substituted phenylthio C₁₋₆ alkyl or optionally substituted phenyl), or a group of Formula SO₂R² (wherein R² is C₁₋₆ alkyl or optionally substituted phenyl);

X is cyano, nitro, halogen, C₁₋₆ alkyl, C₁₋₆ haloalkyl, C₁₋₆ alkoxy, C₁₋₆ haloalkoxy, optionally substituted phenyl or optionally substituted phenoxy; and

n is an integer between 1 and 5], and pest controlling agents containing one or more of the said compounds as active ingredients.

In the above Formula (1),

A is halogen such as fluorine, chlorine, bromine and iodine;

C₁₋₆ alkyl such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, t-butyl, pentyl and its isomers, and hexyl and its isomers;

C₁₋₆ haloalkyl such as chloromethyl, fluoromethyl, bromomethyl, dichloromethyl, difluoromethyl, dibromomethyl, trichloromethyl, trifluoromethyl, tribromomethyl, trichloroethyl, trifluoroethyl and pentafluoroethyl;

C₁₋₆ alkoxy such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, sec-butoxy, isobutoxy and t-butoxy;

optionally substituted C₃₋₆ cycloalkyl such as cyclopropyl, cyclopentyl, 1-methylcyclopentyl, cyclohexyl and 1-methylcyclohexyl;

optionally substituted pyridyl, such as 2-pyridyl, 3-pyridyl and 4-pyridyl that may have substituents at arbitrary positions of the pyridine ring;

thienyl, such as 2-thienyl and 3-thienyl 1 that may have substituents at arbitrary positions of the thiophene ring;

phenyl having substituents at arbitrary positions of the benzene ring; or

phenoxy having optional substituents at arbitrary positions of the benzene ring.

Examples of substituents of the aforementioned pyridyl, thienyl, phenyl and phenoxy groups include halogens such as fluorine and chlorine; C₁₋₆ alkyl such as methyl and ethyl; C₁₋₆ alkoxy such as methoxy, ethoxy and isopropoxy; and nitro. These pyridyl, thienyl, phenyl and phenoxy groups may have two or more, same or different, substituents.

B is hydrogen;

halogen such as fluorine, chlorine, bromine and iodine;

C₁₋₆ alkoxycarbonyl such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl and t-butoxycarbonyl;

C₁₋₆ alkyl such as methyl, ethyl, propyl, isopropyl, butyl, sec-butyl, isobutyl, t-butyl, pentyl and hexyl;

C₁₋₆ haloalkyl such as chloromethyl, fluoromethyl, bromomethyl, dichloromethyl, difluoromethyl, dibromomethyl, trichloromethyl, trifluoromethyl, tribromomethyl, trichloroethyl, trifluoroethyl and pentafluoroethyl; or

C₃₋₆ cycloalkyl such as cyclopropyl, cyclopentyl and cyclohexyl.

R is C₁₋₆ alkyl such as methyl, ethyl, propyl, isopropyl, butyl and t-butyl; or

a group represented by Formula COR¹ or SO₂R²,

wherein R¹ is C₁₋₁₂ alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl and its isomers, hexyl and its isomers, heptyl and its isomers, nonyl and its isomers and dodecyl, and branched alkyl groups are particularly preferred;

C₁₋₆ haloalkyl such as chloromethyl, fluoromethyl, bromomethyl, dichloromethyl, difluoromethyl, dibromomethyl, trichloromethyl, trifluoromethyl, tribromomethyl, trichloroethyl, trifluoroethyl and pentafluoroethyl;

optionally substituted C₃₋₆ cycloalkyl such as cyclopropyl, 1-methylcyclopropyl, cyclopentyl, 1-methylcyclopentyl, cyclohexyl and 1-methylcyclohexyl;

C₁₋₆ alkoxy C₁₋₆ alkyl such as methoxymethyl, methoxyethyl, ethoxymethyl, propoxymethyl and butoxymethyl;

C₁₋₆ alkylthio C₁₋₆ alkyl such as methylthiomethyl, methylthioethyl, ethylthioethyl, ethylthiomethyl, propylthiomethyl and butylthiomethyl;

mono- or di-C₁₋₆ alkylamino such as methylamino, ethylamino, propylamino, dimethylamino, diethylamino, dipropylamino, dibutylamino and ethylisopropylamino;

optionally substituted phenyl C₁₋₆ alkyl, such as benzyl, phenethyl and phenylpropyl that may have substituents at arbitrary positions of the benzene ring;

optionally substituted phenoxy C₁₋₆ alkyl, such as phenoxymethyl and phenoxyethyl that may have substituents at arbitrary positions of the benzene ring;

optionally substituted phenylthio C₁₋₆ alkyl, such as phenylthiomethyl, phenylthioethyl, phenylthiopropyl and phenylthiobutyl that may have substituents at arbitrary positions of the benzene ring; or

phenyl having optional substituents at arbitrary positions of the benzene ring.

R² is C₁₋₆ alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl and its isomers, and hexyl and its isomers, or phenyl having optional substituents at arbitrary positions of the benzene ring.

In these R¹ and R², examples of benzene-ring substituents of the phenyl C₁₋₆ alkyl, phenylthio C₁₋₆ alkyl, phenoxy C₁₋₆ alkyl and phenyl groups include halogen such as fluorine and chlorine, C₁₋₆ alkyl such as methyl and ethyl, C₁₋₆ alkoxy such as methoxy, ethoxy and isopropoxy, and nitro. These benzene rings may have two or more, same or different, substituents.

X is cyano, nitro,

halogen such as chlorine, bromine and fluorine;

C₁₋₆ alkyl such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, s-butyl, t-butyl, pentyl and its isomers, and hexyl and its isomers;

C₁₋₆ haloalkyl such as chloromethyl, fluoromethyl, dichloromethyl, trichloromethyl, trifluoromethyl, 1-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl and pentafluoroethyl;

C₁₋₆ alkoxy such as methoxy, ethoxy, propoxy, isopropoxy and butoxy;

C₁₋₆ haloalkoxy such as chloromethoxy, dichloromethoxy, trichloromethoxy, trifluoromethoxy, 1-fluoroethoxy and 1,1-difluoroethoxy;

optionally substituted phenyl, or

optionally substituted phenoxy.

Examples of substituents of these phenyl and phenoxy groups include halogen such as fluorine and chlorine; C₁₋₆ alkyl such as methyl and ethyl; C₁₋₆ alkoxy such as methoxy, ethoxy and isopropoxy; and nitro. The said phenyl group may have two or more, same or different, substituents.

When n is 2 or larger, X's may be the same or different groups.

Compounds having particularly excellent pest controlling effects among the compounds of the present invention, compared to similar, known cinnamonitrile compounds, are those where, in the above Formula (1), A is C₁₋₆ alkyl, optionally substituted C₃₋₆ cycloalkyl, optionally substituted pyridyl, optionally substituted thienyl or substituted phenyl; B is hydrogen; R is COR¹ or SO₂R²; and X is halogen, C₁₋₆ alkyl, C₁₋₆ haloalkyl or C₁₋₆ alkoxy, and at least one of the substituents is at position 2.

FORMS TO IMPLEMENT THE INVENTION

The compounds of the present invention are prepared, for example, according to the following:

(wherein A, B, R, X and n are as defined above, and L¹ is a leaving group such as halogen, C₁₋₆ alkoxy, phenoxy, 1-imidazolyl, 1-pyrazolyl, p-toluenesulfonyloxy, methanesulfonyloxy or trifluoromethanesulfonyloxy).

That is, 1 mole of a compound of Formula (2) is reacted with 0.5 to 2 moles of a compound of Formula (3) in an inert solvent in the presence of a base, to give a compound of Formula (1).

Examples of bases used for this reaction include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; carbonates such as sodium carbonate and potassium carbonate; organic metals such as n-butyl lithium and lithium diisopropylamide (LDA); and organic bases such as triethylamine, diisopropylethylamine and pyridine.

Solvents able to be used include N,N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), tetrahydrofuran (THF), acetonitrile, hexamethylphosphoramide (HMPT), benzene, toluene, dichloromethane, chloroform and carbon tetrachloride. Preferred reaction temperatures are from −78° C. to the boiling point of solvents used.

The compounds of Formula (1) of the present invention have 2 stereoisomers. One of the isomers or a mixture of the isomers may be produced, depending on reaction conditions and purification methods. These isomers are all covered by the present invention.

A compound of Formula (2) of a starting material can be prepared as follows:

(wherein A, B, X and n are as defined above, and L² is a leaving group such as halogen, C₁₋₆ alkoxy, phenoxy, 1-imidazolyl or 1-pyrazolyl).

That is, 1 mole of a compound of Formula (4) is reacted with 0.5 to 2 moles of a compound of Formula (5) in an inert solvent in the presence of a base, to give a compound of Formula (2).

Examples of bases used for this reaction include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; carbonates such as sodium carbonate and potassium carbonate; organic metals such as n-butyl lithium and LDA; and organic bases such as triethylamine, diisopropylethylamine and pyridine.

Solvents able to be used include DMF, DMSO, THF, acetonitrile, hexamethylphosphoramide (HMPT), benzene, toluene, dichloromethane, chloroform and carbon tetrachloride. Preferred reaction temperatures are from −78° C. to the boiling point of solvents used.

A target compound is obtained with usual post-treatments after the completion of the reaction.

The structures of the compounds of the present invention were determined by IR, MNR, MS and other means.

Representative examples of the compounds of the present invention, that can be prepared according to the above processes, are shown in Tables 1 to 4. The symbols used in the tables have the following meanings:

Me: methyl, Et: ethyl, Pr: propyl, Bu: butyl, Pen: pentyl, Hex: hexyl, Ph: phenyl, n: normal, i: iso, t: tertiary, neo: neo, and c: cyclo

TABLE 1

X₁ X₂ R X₁ X₂ R X₁ X₂ R X₁ X₂ R CF₃ H COtBu CF₃ H R21 Me H CO₂CH₂Ph Me H R31 CF₃ H COMe CF₃ H R22 Me H CONMe₂ Me H R32 CF₃ H COEt CF₃ H R23 Me H R1 Me H R33 CF₃ H COnPr CF₃ H R24 Me H R2 Me H R34 CF₃ H COnBu CF₃ H R25 Me H R3 Me H R35 CF₃ H COPh CF₃ H R26 Me H R4 Me H Me CF₃ H COCCl₃ CF₃ H R27 Me H R5 Me H CH₃Ph CF₃ H COCF₃ CF₃ H R28 Me H R6 Me H SO₂Me CF₃ H CO₂Me CF₃ H R29 Me H R7 Me H SO₂Et CF₃ H CO₂nBu CF₃ H R30 Me H R8 Me H SO₂nPr CF₃ H CO₂CH₂Ph CF₃ H R31 Me H R9 Me H SO₂iPr CF₃ H CONMe₂ CF₃ H R32 Me H R10 Me H R36 CF₃ H R1 CF₃ H R33 Me H R11 Cl H COtBu CF₃ H R2 CF₃ H R34 Me H R12 Cl H COMe CF₃ H R3 CF₃ H R35 Me H R13 Cl H COEt CF₃ H R4 CF₃ H Me Me H R14 Cl H COnPr CF₃ H R5 CF₃ H CH₂Ph Me H R15 Cl H COnBu CF₃ H R6 CF₃ H SO₂Me Me H R16 Cl H COPh CF₃ H R7 CF₃ H SO₂Et Me H R17 Cl H COCCl₃ CF₃ H R8 CF₃ H SO₂nPr Me H R18 Cl H COCF₃ CF₃ H R9 CF₃ H SO₂iPr Me H R19 Cl H CO₂Me CF₃ H R10 CF₃ H R36 Me H R20 Cl H CO₂nBu CF₃ H R11 Me H COtBu Me H R21 Cl H CO₂CH₂Ph CF₃ H R12 Me H COMe Me H R22 Cl H CONMe₂ CF₃ H R13 Me H COEt Me H R23 Cl H R1 CF₃ H R14 Me H COnPr Me H R24 Cl H R2 CF₃ H R15 Me H COnBu Me H R25 Cl H R3 CF₃ H R16 Me H COPh Me H R26 Cl H R4 CF₃ H R17 Me H COCCl₄ Me H R27 Cl H R5 CF₃ H R18 Me H COCF₄ Me H R28 Cl H R6 CF₃ H R19 Me H CO₂Me Me H R29 Cl H R7 CF₃ H R20 Me H CO₂nBu Me H R30 Cl H R8 Cl H R9 Cl H SO₂iPr Br H R19 I H COPh Cl H R10 Cl H R36 Br H R20 CN H COtBu Cl H R11 Br H COtBu Br H R21 CN H COMe Cl H R12 Br H COMe Br H R22 CN H COPh Cl H R13 Br H COEt Br H R23 CO₂Me H COtBu Cl H R14 Br H COnPr Br H R24 CO₂Me H COMe Cl H R15 Br H COnBu Br H R25 CO₂Me H COPh Cl H R16 Br H COPh Br H R26 CO₂Et H COtBu Cl H R17 Br H COCCl₃ Br H R27 CO₂Et H COMe Cl H R18 Br H COCF₄ Br H R28 CO₂Et H COPh Cl H R19 Br H CO₂Me Br H R29 Et H COtBu Cl H R20 Br H CO₂nBu Br H R30 Et H COMe Cl H R21 Br H CO₂CH₂Ph Br H R31 Et H COPh Cl H R22 Br H CONMe₂ Br H R32 iPr H COtBu Cl H R23 Br H R1 Br H R33 iPr H COMe Cl H R24 Br H R2 Br H R34 iPr H COPh Cl H R25 Br H R3 Br H R35 CH₂CF₃ H COtBu Cl H R26 Br H R4 Br H Me CH₂CF₃ H COMe Cl H R27 Br H R5 Br H CH₂Ph CH₂CF₃ H COPh Cl H R28 Br H R6 Br H SO₂Me OMe H COtBu Cl H R29 Br H R7 Br H SO₂Et OMe H COMe Cl H R30 Br H R8 Br H SO₂nPr OMe H COPh Cl H R31 Br H R9 Br H SO₂iPr OEt H COtBu Cl H R32 Br H R10 Br H R36 OEt H COMe Cl H R33 Br H R11 F H COtBu OEt H COPh Cl H R34 Br H R12 F H COMe OiPr H COtBu Cl H R35 Br H R13 F H COPh OiPr H COMe Cl H Me Br H R14 F H R1 OiPr H COPh Cl H CH₂Ph Br H R15 F H R2 OCF₃ H COtBu Cl H SO₂Me Br H R16 F H R25 OCF₃ H COMe Cl H SO₂Et Br H R17 I H COtBu OCF₃ H COPh Cl H SO₂nPr Br H R18 I H COMe OPh H COtBu OPh H COMe F F R19 F Me CO₂Me F Me R29 OPh H COPh F F R20 F Me CO₂nBu F Me R30 F F COtBu F F R21 F Me CO₂CH₂Ph F Me R31 F F COMe F F R22 F Me CONMe₂ F Me R32 F F COEt F F R23 F Me R1 F Me R33 F F COnPr F F R24 F Me R2 F Me R34 F F COnBu F F R25 F Me R3 F Me R35 F F COPh F F R26 F Me R4 F Me Me F F COCCl₃ F F R27 F Me R5 F Me CH₂Ph F F COCF₃ F F R28 F Me R6 F Me SO₂Me F F CO₂Me F F R29 F Me R7 F Me SO₂Et F F CO₂nBu F F R30 F Me R8 F Me SO₂nPr F F CO₂CH₂Ph F F R31 F Me R9 F Me SO₂iPr F F CONMe₂ F F R32 F Me R10 F Me R36 F F R1 F F R33 F Me R11 F Cl COtBu F F R2 F F R34 F Me R12 F Cl COMe F F R3 F F R35 F Me R13 F Cl COEt F F R4 F F Me F Me R14 F Cl COnPr F F R5 F F CH₂Ph F Me R15 F Cl COnBu F F R6 F F SO₂Me F Me R16 F Cl COPh F F R7 F F SO₂Et F Me R17 F Cl COCCl₃ F F R8 F F SO₂nPr F Me R18 F Cl COCF₃ F F R9 F F SO₃iPr F Me R19 F Cl CO₂Me F F R10 F F R36 F Me R20 F Cl CO₂nBu F F R11 F Me COtBu F Me R21 F Cl CO₂CH₂Ph F F R12 F Me COMe F Me R22 F Cl CONMe₂ F F R13 F Me COEt F Me R23 F Cl R1 F F R14 F Me COnPr F Me R24 F Cl R2 F F R15 F Me COnBu F Me R25 F Cl R3 F F R16 F Me COPh F Me R26 F Cl R4 F F R17 F Me COCCl₃ F Me R27 F Cl R5 F F R18 F Me COCF₃ F Me R28 F Cl R6 F Cl R7 F Cl SO₂Et CH₂F H CO₂CH₂Ph CH₂F H R31 F Cl R8 F Cl SOnPr CH₂F H CONMe₂ CH₂F H R32 F Cl R9 F Cl SO₂iPr CH₂F H R1 CH₂F H R33 F Cl R10 F Cl R36 CH₂F H R2 CH₂F H R34 F Cl R11 F OMe COtBu CH₂F H R3 CH₂F H R35 F Cl R12 F OMe COMe CH₂F H R4 CH₂F H Me F Cl R13 F OMe COPh CH₂F H R5 CH₂F H CH₂Ph F Cl R14 F CF₃ COtBu CH₂F H R6 CH₂F H SO₂Me F Cl R15 F CF₃ COMe CH₂F H R7 CH₂F H SO₂Et F Cl R16 F CF₃ COPh CH₂F H R8 CH₂F H SO₂nPr F Cl R17 Cl Cl COtBu CH₂F H R9 CH₂F H SO₂iPr F Cl R18 Cl Cl COMe CH₂F H R10 CH₂F H R36 F Cl R19 Cl Cl COPh CH₂F H R11 F Cl R20 Cl Me COtBu CH₂F H R12 F Cl R21 Cl Me COMe CH₂F H R13 F Cl R22 Cl Me COPh CH₂F H R14 F Cl R23 Me Me COtBu CH₂F H R15 F Cl R24 Me Me COMe CH₂F H R16 F Cl R25 Me Me COPh CH₂F H R17 F Cl R26 OMe OMe COtBu CH₂F H R18 F Cl R27 OMe OMe COMe CH₂F H R19 F Cl R28 OMe OMe COPh CH₂F H R20 F Cl R29 CH₂F H COtBu CH₂F H R21 F Cl R30 CH₂F H COMe CH₂F H R22 F Cl R31 CH₂F H COEt CH₂F H R23 F Cl R32 CH₂F H COnPr CH₂F H R24 F Cl R33 CH₂F H COnBu CH₂F H R25 F Cl R34 CH₂F H COPh CH₂F H R26 F Cl R35 CH₂F H COCCl₃ CH₂F H R27 F Cl Me CH₂F H COCF₃ CH₂F H R28 F Cl CH₂Ph CH₂F H CO₂Me CH₂F H R29 F Cl SO₂Me CH₂F H CO₂nBu CH₂F H R30

TABLE 2

Y X₁ X₂ R F CF₃ H COtBu F CF₃ H COMe F CF₃ H COEt F CF₃ H COnPr F CF₃ H COnBu F CF₃ H COPh F CF₃ H COCCl₃ F CF₃ H COCF₃ F CF₃ H CO₂Me F CF₃ H CO₂nBu F CF₃ H CO₂CH₂Ph F CF₃ H CONMe₂ F CF₃ H R1 F CF₃ H R2 F CF₃ H R3 F CF₃ H R4 F CF₃ H R5 F CF₃ H R6 F CF₃ H R7 F CF₃ H R8 F CF₃ H R9 F CF₃ H R10 F CF₃ H R11 F CF₃ H R12 F CF₃ H R13 F CF₃ H R14 F CF₃ H R15 F CF₃ H R16 F CF₃ H R17 F CF₃ H R18 F CF₃ H R19 F CF₃ H R20 F CF₃ H R21 F CF₃ H R22 F CF₃ H R23 F CF₃ H R24 F CF₃ H R25 F CF₃ H R26 F CF₃ H R27 F CF₃ H R28 F CF₃ H R29 F CF₃ H R30 F CF₃ H R31 F CF₃ H R32 F CF₃ H R33 F CF₃ H R34 F CF₃ H R35 F CF₃ H Me F CF₃ H CH₂Ph F CF₃ H SO₂Me F CF₃ H SO₂Et F CF₃ H SO₂nPr F CF₃ H SO₂iPr F CF₃ H R36 F Me H COtBu F Me H COMe F Me H COEt F Me H COnPr F Me H COnBu F Me H COPh F Me H COCCl₃ F Me H COCF₃ F Me H CO₂Me F Me H CO₂nBu F Me H CO₂CH₂Ph F Me H CONMe₂ F Me H R1 F Me H R2 F Me H R3 F Me H R4 F Me H R5 F Me H R6 F Me H R7 F Me H R8 F Me H R9 F Me H R10 F Me H R11 F Me H R12 F Me H R13 F Me H R14 F Me H R15 F Me H R16 F Me H R17 F Me K R18 F Me H R19 F Me H R20 F Me H R21 F Me H R22 F Me H R23 F Me H R24 F Me H R25 F Me H R26 F Me H R27 F Me H R28 F Me H R29 F Me H R30 F Me H R31 F Me H R32 F Me H R33 F Me H R34 F Me H R35 F Me H Me F Me H CH₂Ph F Me H SO₂Me F Me H SO₂Et F Me H SO₂nPr F Me H SO₂iPr F Me H R36 F Cl H COtBu F Cl H COMe F Cl H COEt F Cl H COnPr F Cl H COnBu F Cl H COPh F Cl H COCCl₃ F Cl H COCF₃ F Cl H CO₂Me F Cl H CO₂nBu F Cl H CO₂CH₂Ph F Cl H CONMe₂ F Cl H R1 F Cl H R2 F Cl H R3 F Cl H R4 F Cl H R5 F Cl H R6 F Cl H R7 F Cl H R8 F Cl H R9 F Cl H R10 F Cl H R11 F Cl H R12 F Cl H R13 F Cl H R14 F Cl H R15 F Cl H R16 F Cl H R17 F Cl H R18 F Cl H R19 F Cl H R20 F Cl H R21 F Cl H R22 F Cl H R23 F Cl H R24 F Cl H R25 F Cl H R26 F Cl H R27 F Cl H R28 F Cl H R29 F Cl H R30 F Cl H R31 F Cl H R32 F Cl H R33 F Cl H R34 F Cl H R35 F Cl H Me F Cl H CH₂Ph F Cl H SO₂Me F Cl H SO₂Et F Cl H SO₂nPr F Cl H SO₂iPr F Cl H R36 F Br H COtBu F Br H COMe F Br H COEt F Br H COnPr F Br H COnBu F Br H COPh F Br H COCCl₃ F Br H COCF₃ F Br H CO₂Me F Br H CO₂nBu F Br H CO₂CH₂Ph F Br H CONMe₂ F Br H R1 F Br H R2 F Br H R3 F Br H R4 F Br H R5 F Br H R6 F Br H R7 F Br H R8 F Br H R9 F Br H R10 F Br H R11 F Br H R12 F Br H R13 F Br H R14 F Br H R15 F Br H R16 F Br H R17 F Br H R18 F Br H R19 F Br H R20 F Br H R21 F Br H R22 F Br H R23 F Br H R24 F Br H R25 F Br H R26 F Br H R27 F Br H R28 F Br H R29 P Br H R30 F Br H R31 F Br H R32 P Br H R33 F Br H R34 F Br H R35 F Br H Me F Br H CH₂Ph F Br H SO₂Me F Br H SO₂Et F Br H SO₂nPr F Br H SO₂iPr F Br H R36 F F H COtBu F F H COMe F F H COPh F F H R1 F F H R2 F F H R25 F I H COtBu F I H COMe F I H COPh F CN H COtBu F CN H COMe F CN H COPh F CO₂Me H COtBu F CO₂Me H COMe F CO₂Me H COPh F CO₂Et H COtBu F CO₂Et H COMe F CO₂Et H COPh F Et H COtBu F Et H COMe F Et H COPh F iPr H COtBu F iPr H COMe F iPr H COPh F CH₂CF₃ H COtBu F CH₂CF₃ H COMe F CH₂CF₃ H COPh F OMe H COtBu F OMe H COMe F OMe H COPh F OEt H COtBu F OEt H COMe F OEt H COPh F OiPr H COtBu F OiPr H COMe F OiPr H COPh F OCF₃ H COtBu F OCF₃ H COMe F OCF₃ H COPh F OPh H COtBu F OPh H COMe F OPh H COPh F F F COtBu F F F COMe F F F COEt F F F COnPr F F F COnBu F F F COPh F F F COCCl₃ F F F COCF₃ F F F CO₂Me F F F CO₂Bu F F F CO₂CH₂Ph F F F CONMe₂ F F F R1 F F F R2 F F F R3 F F F R4 F F F R5 F F F R6 F F F R7 F F F R8 F F F R9 F F F R10 F F F R11 F F F R12 F F F R13 F F F R14 F F F R15 F F F R16 F F F R17 F F F R18 F F F R19 F F F R20 F F F R21 F F F R22 F F F R23 F F F R24 P F F R25 P F F R26 F F F R27 F F F R28 F F F R29 F F F R30 F F F R31 F F F R32 F F F R33 F F F R34 F F F R35 F F F Me F F F CH₂Ph F F F SO₂Me F F F SO₂Et F F F SO₂nPr F F F SO₂iPr F F F R36 F F Me COtBu F F Me COMe F F Me COEt F F Me COnPr F F Me COnBu F F Me COPh F F Me COCCl₃ F F Me COCF₃ F F Me CO₂Me F F Me CO₂nBu F F Me CO₂CH₂Ph F F Me CONMe₂ F F Me R1 F F Me R2 F F Me R3 F F Me R4 F F Me R5 F F Me R6 F F Me R7 F F Me R8 F F Me R9 F F Me R10 F F Me R11 F F Me R12 F F Me R13 F F Me R14 F F Me R15 F F Me R16 F F Me R17 F F Me R18 F F Me R19 F F Me R20 F F Me R21 F F Me R22 F F Me R23 F F Me R24 F F Me R25 F F Me R26 F F Me R27 F F Me R28 F F Me R29 F F Me R30 F F Me R31 F F Me R32 F F Me R33 F F Me R34 F F Me R35 F F Me Me F F Me CH₂Ph F F Me SO₂Me F F Me SO₂Et F F Me SO₂nPr F F Me SO₂iPr F F Me R36 F F Cl COtBu F F Cl COMe F F Cl COEt F F Cl COnPr F F Cl COnBu F F Cl COPh F F Cl COCCl₃ F F Cl COCF₃ F F Cl CO₂Me F F Cl CO₂nBu F F Cl CO₂CH₂Ph F F Cl CONMe₂ F F Cl R1 F F Cl R2 F F Cl R3 F F Cl R4 F F Cl R5 F F Cl R6 F F Cl R7 F F Cl R8 F F Cl R9 F F Cl R10 F F Cl R11 F F Cl R12 F F Cl R13 F F Cl R14 F F Cl R15 F F Cl R16 F F Cl R17 F F Cl R18 F F Cl R19 F F Cl R20 F F Cl R21 F F Cl R22 F F Cl R23 F F Cl R24 F F Cl R25 F F Cl R26 F F Cl R27 F F Cl R28 F F Cl R29 F F Cl R30 F F Cl R31 F F Cl R32 F F Cl R33 F F Cl R34 F F Cl R35 F F Cl Me F F Cl CH₂Ph F F Cl SO₂Me F F Cl SO₂Et F F Cl SO₂nPr F F Cl SO₂iPr F F Cl R36 F F OMe COtBu F F OMe COMe F F OMe COPh F F CF₃ COtBu F F CF₃ COMe F F CF₃ COPh F Cl Cl COtBu F Cl Cl COMe F Cl Cl COPh F Cl Me COtBu F Cl Me COMe F Cl Me COPh F Me Me COtBu F Me Me COMe F Me Me COPh F OMe OMe COtBu F OMe OMe COMe F OMe OMe COPh Me CF₃ H COtBu Me CF₃ H COMe Me CF₃ H COEt Me CF₃ H COnPr Me CF₃ H COnBu Me CF₃ H COPh Me CF₃ H COCCl₃ Me CF₃ H COCF₃ Me CF₃ H CO₂Me Me CF₃ H CO₂nBu Me CF₃ H CO₂CH₂Ph Me CF₃ H CONMe₂ Me CF₃ H R1 Me CF₃ H R2 Me CF₃ H R3 Me CF₃ H R4 Me CF₃ H R5 Me CF₃ H R6 Me CF₃ H R7 Me CF₃ H R8 Me CF₃ H R9 Me CF₃ H R10 Me CF₃ H R11 Me CF₃ H R12 Me CF₃ H R13 Me CF₃ H R14 Me CF₃ H R15 Me CF₃ H R16 Me CF₃ H R17 Me CF₃ H R18 Me CF₃ H R19 Me CF₃ H R20 Me CF₃ H R21 Me CF₃ H R22 Me CF₃ H R23 Me CF₃ H R24 Me CF₃ H R25 Me CF₃ H R26 Me CF₃ H R27 Me CF₃ H R28 Me CF₃ H R29 Me CF₃ H R30 Me CF₃ H R31 Me CF₃ H R32 Me CF₃ H R33 Me CF₃ H R34 Me CF₃ H R35 Me CF₃ H Me Me CF₃ H CH₂Ph Me CF₃ H SO₂Me Me CF₃ H SO₂Et Me CF₃ H SO₂nPr Me CF₃ H SO₂iPr Me CF₃ H R36 Me Me H COtBu Me Me H COMe Me Me H COEt Me Me H COnPr Me Me H COnBu Me Me H COPh Me Me H COCCl₃ Me Me H COCF₃ Me Me H CO₂Me Me Me H CO₂tBu Me Me H CO₂CH₂Ph Me Me H CONMe₂ Me Me H R1 Me Me H R2 Me Me H R3 Me Me H R4 Me Me H R5 Me Me H R6 Me Me H R7 Me Me H R8 Me Me H R9 Me Me H R10 Me Me H R11 Me Me H R12 Me Me H R13 Me Me H R14 Me Me H R15 Me Me H R16 Me Me H R17 Me Me H R18 Me Me H R19 Me Me H R20 Me Me H R21 Me Me H R22 Me Me H R23 Me Me H R24 Me Me H R25 Me Me H R26 Me Me H R27 Me Me H R28 Me Me H R29 Me Me H R30 Me Me H R31 Me Me H R32 Me Me H R33 Me Me H R34 Me Me H R35 Me Me H Me Me Me H CH₂Ph Me Me H SO₂Me Me Me H SO₂Et Me Me H SO₂nPr Me Me H SO₂iPr Me Me H R36 Me Cl H COtBu Me Cl H COMe Me Cl H COEt Me Cl H COnPr Me Cl H COnBu Me Cl H COPh Me Cl H COCCl₃ Me Cl H COCF₃ Me Cl H CO₂Me Me Cl H CO₂nBu Me Cl H CO₂CH₂Ph Me Cl H CONMe₂ Me Cl H R1 Me Cl H R2 Me Cl H R3 Me Cl H R4 Me Cl H R5 Me Cl H R6 Me Cl H R7 Me Cl H R8 Me Cl H R9 Me Cl H R10 Me Cl H R11 Me Cl H R12 Me Cl H R13 Me Cl H R14 Me Cl H R15 Me Cl H R16 Me Cl H R17 Me Cl H R18 Me Cl H R19 Me Cl H R20 Me Cl H R21 Me Cl H R22 Me Cl H R23 Me Cl H R24 Me Cl H R25 Me Cl H R26 Me Cl H R27 Me Cl H R28 Me Cl H R29 Me Cl H R30 Me Cl H R31 Me Cl H R32 Me Cl H R33 Me Cl H R34 Me Cl H R35 Me Cl H Me Me Cl H CH₂Ph Me Cl H SO₂Me Me Cl H SO₂Et Me Cl H SO₂nPr Me Cl H SO₂iPr Me Cl H R36 Me Br H COtBu Me Br H COMe Me Br H COtBu Me F H COtBu Me F H COMe Me F H COtBu Me I H COtBu Me I H COMe Me I H COPh Me CN H COtBu Me CN H COMe Me CN H COPh Me CO₂Me H COtBu Me CO₂Me H COMe Me CO₂Me H COPh Me CO₂Et H COtBu Me CO₂Et H COMe Me CO₂Et H COPh Me Et H COtBu Me Et H COMe Me Et H COPh Me iPr H COtBu Me iPr H COMe Me iPr H COPh Me CH₂CF₃ H COtBu Me CH₂CF₃ H COMe Me CH₂CF₃ H COPh Me OMe H COtBu Me OMe H COMe Me OMe H COPh Me OEt H COtBu Me OEt H COMe Me OEt H COPh Me OiPr H COtBu Me OiPr H COMe Me OiPr H COPh Me OCF₃ H COtBu Me OCF₃ H COMe Me OCF₃ H COPh Me OPh H COtBu Me OPh H COMe Me OPh H COPh Me F F COtBu Me F F COMe Me F F COEt Me F F COnPr Me F F COnBu Me F F COPh Me F F COCCl₃ Me F F COCF₃ Me F F CO₂Me Me F F CO₂nBu Me F F CO₂CH₂Ph Me F F CONMe₂ Me F F R1 Me F F R2 Me F F R3 Me F F R4 Me F F R5 Me F F R6 Me F F R7 Me F F R8 Me F F R9 Me F F R10 Me F F R11 Me F F R12 Me F F R13 Me F F R14 Me F F R15 Me F F R16 Me F F R17 Me F F R18 Me F F R19 Me F F R20 Me F F R21 Me F F R22 Me F F R23 Me F F R24 Me F F R25 Me F F R26 Me F F R27 Me F F R28 Me F F R29 Me F F R30 Me F F R31 Me F F R32 Me F F R33 Me F F R34 Me F F R35 Me F F Me Me F F CH₂Ph Me F F SO₂Me Me F F SO₂Et Me F F SO₂nPr Me F F SO₂iPr Me F F R36 Me F Me COtBu Me F Me COMe Me F Me COEt Me F Me COnPr Me F Me COnBu Me F Me COPh Me F Me COCCl₃ Me F Me COCF₃ Me F Me CO₂Me Me F Me CO₂nBu Me F Me CO₂CH₂Ph Me F Me CONMe₂ Me F Me R1 Me F Me R2 Me F Me R3 Me F Me R4 Me F Me R5 Me F Me R6 Me F Me R7 Me F Me R8 Me F Me R9 Me F Me R10 Me F Me R11 Me F Me R12 Me F Me R13 Me F Me R14 Me F Me R15 Me F Me R16 Me F Me R17 Me F Me R18 Me F Me R19 Me F Me R20 Me F Me R21 Me F Me R22 Me F Me R23 Me F Me R24 Me F Me R25 Me F Me R26 Me F Me R27 Me F Me R28 Me F Me R29 Me F Me R30 Me F Me R31 Me F Me R32 Me F Me R33 Me F Me R34 Me F Me R35 Me F Me Me Me F Me CH₂Ph Me F Me SO₂Me Me F Me SO₂Et Me F Me SO₂nPr Me F Me SO₂iPr Me F Me R36 Me F Cl COtBu Me F Cl COMe Me F Cl COEt Me F Cl COnPr Me F Cl COnBu Me F Cl COPh Me F Cl COCCl₃ Me F Cl COCF₃ Me F Cl CO₂Me Me F Cl CO₂nBu Me F Cl CO₂CH₂Ph Me F Cl CONMe₂ Me F Cl R1 Me F Cl R2 Me F Cl R3 Me F Cl R4 Me F Cl R5 Me F Cl R6 Me F Cl R7 Me F Cl R8 Me F Cl R9 Me F Cl R10 Me F Cl R11 Me F Cl R12 Me F Cl R13 Me F Cl R14 Me F Cl R15 Me F Cl R16 Me F Cl R17 Me F Cl R18 Me F Cl R19 Me F Cl R20 Me F Cl R21 Me F Cl R22 Me F Cl R23 Me F Cl R24 Me F Cl R25 Me F Cl R26 Me F Cl R27 Me F Cl R28 Me F Cl R29 Me F Cl R30 Me F Cl R31 Me F Cl R32 Me F Cl R33 Me F Cl R34 Me F Cl R35 Me F Cl Me Me F Cl CH₂Ph Me F Cl SO₂Me Me F Cl SO₂Et Me F Cl SO₂nPr Me F Cl SO₂iPr Me F Cl R36 Me F OMe COtBu Me F OMe COMe Me F OMe COPh Me F CF₃ COtBu Me F CF₃ COMe Me F CF₃ COPh Me Cl Cl COtBu Me Cl Cl COMe Me Cl Cl COPh Me Cl Me COtBu Me Cl Me COMe Me Cl Me COPh Me Me Me COtBu Me Me Me COMe Me Me Me COPh Me OMe OMe COtBu Me OMe OMe COMe Me OMe OMe COPh Cl CF₃ H COtBu Cl CF₃ H COMe Cl CF₃ H COEt Cl CF₃ H COnPr Cl CF₃ H COnBu Cl CF₃ H COPh Cl CF₃ H COCCl₃ Cl CF₃ H COCF₃ Cl CF₃ H CO₂Me Cl CF₃ H CO₂nBu Cl CF₃ H CO₂CH₂Ph Cl CF₃ H CONMe₂ Cl CF₃ H R1 Cl CF₃ H R2 Cl CF₃ H R3 Cl CF₃ H R4 Cl CF₃ H R5 Cl CF₃ H R6 Cl CF₃ H R7 Cl CF₃ H R8 Cl CF₃ H R9 Cl CF₃ H R10 Cl CF₃ H R11 Cl CF₃ H R12 Cl CF₃ H R13 Cl CF₃ H R14 Cl CF₃ H R15 Cl CF₃ H R16 Cl CF₃ H R17 Cl CF₃ H R18 Cl CF₃ H R19 Cl CF₃ H R20 Cl CF₃ H R21 Cl CF₃ H R22 Cl CF₃ H R23 Cl CF₃ H R24 Cl CF₃ H R25 Cl CF₃ H R26 Cl CF₃ H R27 Cl CF₃ H R28 Cl CF₃ H R29 Cl CF₃ H R30 Cl CF₃ H R31 Cl CF₃ H R32 Cl CF₃ H R33 Cl CF₃ H R34 Cl CF₃ H R35 Cl CF₃ H Me Cl CF₃ H CH₂Ph Cl CF₃ H SO₂Me Cl CF₃ H SO₂Et Cl CF₃ H SO₂nPr Cl CF₃ H SO₂iPr Cl CF₃ H R36 Cl Me H COtBu Cl Me H COMe Cl Me H COEt Cl Me H COnPr Cl Me H COnBu Cl Me H COPh Cl Me H COCCl₃ Cl Me H COCF₃ Cl Me H CO₂Me Cl Me H CO₂nBu Cl Me H CO₂CH₂Ph Cl Me H CONMe₂ Cl Me H R1 Cl Me H R2 Cl Me H R3 Cl Me H R4 Cl Me H R5 Cl Me H R6 Cl Me H R7 Cl Me H R8 Cl Me H R9 Cl Me H R10 Cl Me H R11 Cl Me H R12 Cl Me H R13 Cl Me H R14 Cl Me H R15 Cl Me H R16 Cl Me H R17 Cl Me H R18 Cl Me H R19 Cl Me H R20 Cl Me H R21 Cl Me H R22 Cl Me H R23 Cl Me H R24 Cl Me H R25 Cl Me H R26 Cl Me H R27 Cl Me H R28 Cl Me H R29 Cl Me H R30 Cl Me H R31 Cl Me H R32 Cl Me H R33 Cl Me H R34 Cl Me H R35 Cl Me H Me Cl Me H CH₂Ph Cl Me H SO₂Me Cl Me H SO₂Et Cl Me H SO₂nPr Cl Me H SO₂iPr Cl Me H R36 Cl Cl H COtBu Cl Cl H COMe Cl Cl H COEt Cl Cl H COnPr Cl Cl H COnBu Cl Cl H COPh Cl Cl H COCCl₃ Cl Cl H COCF₃ Cl Cl H CO₂Me Cl Cl H CO₂nBu Cl Cl H CO₂CH₂Ph Cl Cl H CONMe₂ Cl Cl H R1 Cl Cl H R2 Cl Cl H R3 Cl Cl H R4 Cl Cl H R5 Cl Cl H R6 Cl Cl H R7 Cl Cl H R8 Cl Cl H R9 Cl Cl H R10 Cl Cl H R11 Cl Cl H R12 Cl Cl H R13 Cl Cl H R14 Cl Cl H R15 Cl Cl H R16 Cl Cl H R17 Cl Cl H R18 Cl Cl H R19 Cl Cl H R20 Cl Cl H R21 Cl Cl H R22 Cl Cl H R23 Cl Cl H R24 Cl Cl H R25 Cl Cl H R26 Cl Cl H R27 Cl Cl H R28 Cl Cl H R29 Cl Cl H R30 Cl Cl H R31 Cl Cl H R32 Cl Cl H R33 Cl Cl H R34 Cl Cl H R35 Cl Cl H Me Cl Cl H CH₂Ph Cl Cl H SO₂Me Cl Cl H SO₂Et Cl Cl H SO₂nPr Cl Cl H SO₂iPr Cl Cl H R36 Cl Br H CO₂tBu Cl Br H COMe Cl Br H COtBu Cl F H COtBu Cl F H COMe Cl F H COtBu Cl I H COtBu Cl I H COMe Cl I H COPh Cl CN H COtBu Cl CN H COMe Cl CN H COPh Cl CO₂Me H COtBu Cl CO₂Me H COMe Cl CO₂Me H COPh Cl CO₂Et H COtBu Cl CO₂Et H COMe Cl CO₂Et H COPh Cl Et H COtBu Cl Et H COMe Cl Et H COPh Cl iPr H COtBu Cl iPr H COMe Cl iPr H COPh Cl CH₂CF₃ H COtBu Cl CH₂CF₃ H COMe Cl CH₂CF₃ H COPh Cl OMe H COtBu Cl OMe H COMe Cl OMe H COPh Cl OEt H COtBu Cl OEt H COMe Cl OEt H COPh Cl OiPr H COtBu Cl OiPr H COMe Cl OiPr H COPh Cl OCF₃ H COtBu Cl OCF₃ H COMe Cl OCF₃ H COPh Cl OPh H COtBu Cl OPh H COMe Cl OPh H COPh Cl F F COtBu Cl F F COMe Cl F F COEt Cl F F COnPr Cl F F COnBu Cl F F COPh Cl F F COCCl₃ Cl F F COCF₃ Cl F F CO₂Me Cl F F CO₂nBu Cl F F CO₂CH₂Ph Cl F F CONMe₂ Cl F F R1 Cl F F R2 Cl F F R3 Cl F F R4 Cl F F R5 Cl F F R6 Cl F F R7 Cl F F R8 Cl F F R9 Cl F F R10 Cl F F R11 Cl F F R12 Cl F F R13 Cl F F R14 Cl F F R15 Cl F F R16 Cl F F R17 Cl F F R18 Cl F F R19 Cl F F R20 Cl F F R21 Cl F F R22 Cl F F R23 Cl F F R24 Cl F F R25 Cl F F R26 Cl F F R27 Cl F F R28 Cl F F R29 Cl F F R30 Cl F F R31 Cl F F R32 Cl F F R33 Cl F F R34 Cl F F R35 Cl F F Me Cl F F CH₂Ph Cl F F SO₂Me Cl F F SO₂Et Cl F F SO₂nPr Cl F F SO₂iPr Cl F F R36 Cl F Me COtBu Cl F Me COMe Cl F Me COEt Cl F Me COnPr Cl F Me COnBu Cl F Me COPh Cl F Me COCCl₃ Cl F Me COCF₃ Cl F Me CO₂Me Cl F Me CO₂nBu Cl F Me CO₂CH₂Ph Cl F Me CONMe₂ Cl F Me R1 Cl F Me R2 Cl F Me R3 Cl F Me R4 Cl F Me R5 Cl F Me R6 Cl F Me R7 Cl F Me R8 Cl F Me R9 Cl F Me R10 Cl F Me R11 Cl F Me R12 Cl F Me R13 Cl F Me R14 Cl F Me R15 Cl F Me R16 Cl F Me R17 Cl F Me R18 Cl F Me R19 Cl F Me R20 Cl F Me R21 Cl F Me R22 Cl F Me R23 Cl F Me R24 Cl F Me R25 Cl F Me R26 Cl F Me R27 Cl F Me R28 Cl F Me R29 Cl F Me R30 Cl F Me R31 Cl F Me R32 Cl F Me R33 Cl F Me R34 Cl F Me R35 Cl F Me Me Cl F Me CH₂Ph Cl F Me SO₂Me Cl F Me SO₂Et Cl F Me SO₂nPr Cl F Me SO₂iPr Cl F Me R36 Cl F Cl COtBu Cl F Cl COMe Cl F Cl COEt Cl F Cl COnPr Cl F Cl COnBu Cl F Cl COPh Cl F Cl COCCl₃ Cl F Cl COCF₃ Cl F Cl CO₂Me Cl F Cl CO₂nBu Cl F Cl CO₂CH₂Ph Cl F Cl CONMe₂ Cl F Cl R1 Cl F Cl R2 Cl F Cl R3 Cl F Cl R4 Cl F Cl R5 Cl F Cl R6 Cl F Cl R7 Cl F Cl R8 Cl F Cl R9 Cl F Cl R10 Cl F Cl R11 Cl F Cl R12 Cl F Cl R13 Cl F Cl R14 Cl F Cl R15 Cl F Cl R16 Cl F Cl R17 Cl F Cl R18 Cl F Cl R19 Cl F Cl R20 Cl F Cl R21 Cl F Cl R22 Cl F Cl R23 Cl F Cl R24 Cl F Cl R25 Cl F Cl R26 Cl F Cl R27 Cl F Cl R28 Cl F Cl R29 Cl F Cl R30 Cl F Cl R31 Cl F Cl R32 Cl F Cl R33 Cl F Cl R34 Cl F Cl R35 Cl F Cl Me Cl F Cl CH₂Ph Cl F Cl SO₂Me Cl F Cl SO₂Et Cl F Cl SO₂nPr Cl F Cl SO₂iPr Cl F Cl R36 Cl F OMe COtBu Cl F OMe COMe Cl F OMe COPh Cl F CF₃ COtBu Cl F CF₃ COMe Cl F CF₃ COPh Cl Cl Cl COtBu Cl Cl Cl COMe Cl Cl Cl COPh Cl Cl Me COtBu Cl Cl Me COMe Cl Cl Me COPh Cl Me Me COtBu Cl Me Me COMe Cl Me Me COPh Cl OMe OMe COtBu Cl OMe OMe COMe Cl OMe OMe COPh Et CF₃ H COtBu Et Me H COtBu Et Cl H COtBu Et F F COtBu Et F Me COtBu Et F Cl COtBu nPr CF₃ H COtBu nPr Me H COtBu nPr Cl H COtBu nPr F F COtBu nPr F Me COtBu nPr F Cl COtBu iPr CF₃ H COtBu iPr Me H COtBu iPr Cl H COtBu iPr F F COtBu iPr F Me COtBu iPr F Cl COtBu nBu CF₃ H COtBu nBu Me H COtBu nBu Cl H COtBu nBu F F COtBu nBu F Me COtBu nBu F Cl COtBu tBu CF₃ H COtBu tBu Me H COtBu tBu Cl H COtBu tBu F F COtBu tBu F Me COtBu tBu F Cl COtBu nHex CF₃ H COtBu nHex Me H COtBu nHex Cl H COtBu nHex F F COtBu nHex F Me COtBu nHex F Cl COtBu cHex CF₃ H COtBu cHex Me H COtBu cHex Cl H COtBu cHex F F COtBu cHex F Me COtBu cHex F Cl COtBu Ph CF₃ H COtBu Ph Me H COtBu Ph Cl H COtBu Ph F F COtBu Ph F Me COtBu Ph F Cl COtBu CF₃ CF₃ H COtBu CF₃ Me H COtBu CF₃ Cl H COtBu CF₃ F F COtBu CF₃ F Me COtBu CF₃ F Cl COtBu CH₂CF₃ CF₃ H COtBu CH₂CF₃ Me H COtBu CH₂CF₃ Cl H COtBu CH₂CF₃ F F COtBu CH₂CF₃ F Me COtBu CH₂CF₃ F Cl COtBu OMe CF₃ H COtBu OMe Me H COtBu OMe Cl H COtBu OMe F F COtBu OMe F Me COtBu OMe F Cl COtBu OEt CF₃ H COtBu OEt Me H COtBu OEt Cl H COtBu OEt F F COtBu OEt F Me COtBu OEt F Cl COtBu OiPr CF₃ H COtBu OiPr Me H COtBu OiPr Cl H COtBu OiPr F F COtBu OiPr F Me COtBu OiPr F Cl COtBu OtBu CF₃ H COtBu OtBu Me H COtBu OtBu Cl H COtBu OtBu F F COtBu OtBu F Me COtBu OtBu F Cl COtBu OPh CF₃ H COtBu OPh Me H COtBu OPh Cl H COtBu OPh F F COtBu OPh F Me COtBu OPh F Cl COtBu OCF₃ CF₃ H COtBu OCF₃ Me H COtBu OCF₃ Cl H COtBu OCF₃ F F COtBu OCF₃ F Me COtBu OCF₃ F Cl COtBu CN CF₃ H COtBu CN Me H COtBu CN Cl H COtBu CN F F COtBu CN F Me COtBu CN F Cl COtBu NO₂ CF₃ H COtBu NO₂ Me H COtBu NO₂ Cl H COtBu NO₂ F F COtBu NO₂ F Me COtBu NO₂ F Cl COtBu F CH₂F H COtBu F CH₂F H COMe F CH₂F H COEt F CH₂F H COnPr F CH₂F H COCF₃ F CH₂F H COPh F CH₂F H CO₂Me F CH₂F H CO₂nBu F CH₂F H R1 F CH₂F H R2 F CH₂F H R3 F CH₂F H R13 F CH₂F H R14 F CH₂F H R19 F CH₂F H R24 F CH₂F H R25 F CH₂F H R26 F CH₂F H R27 F CH₂F H R28 F CH₂F H R29 F CH₂F H R30 F CH₂F H R31 F CH₂F H R32 F CH₂F H R35 F CH₂F H Me F CH₂F H CH₂Ph F CH₂F H SO₂Me F CH₂F H SO₂Et F CH₂F H SO₂nPr F CH₂F H R36

TABLE 3

Xn R Xn R 2-CF₃-3,4-F₂ COtBu 2,3,5-F₃ COtBu 2-CF₃-3,4-F₂ R1 2,3,5-F₃ R1 2-CF₃-3,4-F₂ R2 2,3,5-F₃ R2 2-CF₃-3,5-F₂ COtBu 2,3,6-F₃ COtBu 2-CF₃-3,5-F₂ R1 2,3,6-F₃ R1 2-CF₃-3,5-F₂ R2 2,3,6-F₃ R2 2-CF₃-3,6-F₂ COtBu 2,4,5-F₃ COtBu 2-CF₃-3,6-F₂ R1 2,4,5-F₃ R1 2-CF₃-3,6-F₂ R2 2,4,5-F₃ R2 2-CF₃-4,5-F₂ COtBu 2,4,6-F₃ COtBu 2-CF₃-4,5-F₂ R1 2,4,6-F₃ R1 2-CF₃-4,5-F₂ R2 2,4,6-F₃ R2 2-CF₃-4,6-F₂ COtBu 2-Cl-3,4-F₂ COtBu 2-CF₃-4,6-F₂ R1 2-Cl-3,4-F₂ R1 2-CF₃-4,6-F₂ R2 2-Cl-3,4-F₂ R2 2-CF₃-5,6-F₂ COtBu 2-Cl-3,5-F₂ COtBu 2-CF₃-5,6-F₂ R1 2-Cl-3,5-F₂ R1 2-CF₃-5,6-F₂ R2 2-Cl-3,5-F₂ R2 2-Me-3,4-F₂ COtBu 2-Cl-3,6-F₂ COtBu 2-Me-3,4-F₂ R1 2-Cl-3,6-F₂ R1 2-Me-3,4-F₂ R2 2-Cl-3,6-F₂ R2 2-Me-3,5-F₂ COtBu 2-Cl-4,5-F₂ COtBu 2-Me-3,5-F₂ R1 2-Cl-4,5-F₂ R1 2-Me-3,5-F₂ R2 2-Cl-4,5-F₂ R2 2-Me-3,6-F₂ COtBu 2-Cl-4,6-F₂ COtBu 2-Me-3,6-F₂ R1 2-Cl-4,6-F₂ R1 2-Me-3,6-F₂ R2 2-Cl-4,6-F₂ R2 2-Me-4,5-F₂ COtBu 2-Cl-5,6-F₂ COtBu 2-Me-4,5-F₂ R1 2-Cl-5,6-F₂ R1 2-Me-4,5-F₂ R2 2-Cl-5,6-F₂ R2 2-Me-4,6-F₂ COtBu 2-CF₃-3,4,6-F₃ COtBu 2-Me-4,6-F₂ R1 2-CF₃-3,5,6-F₃ COtBu 2-Me-4,6-F₂ R2 2-CF₃-4-Cl-6-F COtBu 2-Me-5,6-F₂ COtBu 2-Me-3,4,6-F₃ COtBu 2-Me-5,6-F₂ R1 2-Me-3,5,6-F₃ COtBu 2-Me-5,6-F₂ R2 2,3,4,5,6-F₃ COtBu 2,3,4-F₃ COtBu 2-OMe-4,5-F₂ COtBu 2,3,4-F₃ R1 2-OMe-4,5-Cl₂ COtBu 2,3,4-F₃ R2

TABLE 4

A B R 2-CF₃-3-F—Ph H COtBu 2-CF₃-4-F—Ph H COtBu 2-CF₃-5-F—Ph H COtBu 2-F-3-Me—Ph H COtBu 2-F-4-Me—Ph H COtBu 2-F-5-Me—Ph H COtBu 2-F-3-Cl—Ph H COtBu 2-F-4-Cl—Ph H COtBu 2-F-5-Cl—Ph H COtBu 2-Br-3-F—Ph H COtBu 2-Br-4-F—Ph H COtBu 2-Br-5-F—Ph H COtBu 2-OMe-3-F—Ph H COtBu 2-OMe-4-F—Ph H COtBu 2-OMe-5-F—Ph H COtBu 2-OMe-3-Cl—Ph H COtBu 2-OMe-4-Cl—Ph H COtBu 2-OMe-5-Cl—Ph H COtBu 2-CF₃-3,4-F₂—Ph H COtBu 2-CF₃-3,5-F₂—Ph H COtBu 2-CF₃-3,6-F₂—Ph H COtBu 2-CF₃-4,5-F₂—Ph H COtBu 2-CF₃-4,6-F₂—Ph H COtBu 2-CF₃-5,6-F₂—Ph H COtBu 2-Me-3,4-F₂—Ph H COtBu 2-Me-3,5-F₂—Ph H COtBu 2-Me-3,6-F₂—Ph H COtBu 2-Me-4,5-F₂—Ph H COtBu 2-Me-4,6-F₂—Ph H COtBu 2-Me-5,6-F₂—Ph H COtBu 2-Cl-3,4-F₂—Ph H COtBu 2-Cl-3,5-F₂—Ph H COtBu 2-Cl-3,6-F₂—Ph H COtBu 2-Cl-4,5-F₂—Ph H COtBu 2-Cl-4,6-F₂—Ph H COtBu 2-Cl-5,6-F₂—Ph H COtBu 2-CF₃-3,4,6-F₃—Ph H COtBu 2-CF₃-3,5,6-F₃—Ph H COtBu 2-CF₃-4-Cl-6-F—Ph H COtBu 2-Me-3,4,6-F₃—Ph H COtBu 2-Me-3,5,6-F₃—Ph H COtBu 2-OMe-4,5-F₂—Ph H COtBu 2-OMe-4,5-Cl₃—Ph H COtBu 2-Me-cHex H COtBu 2-Me-cHex H R1 2-Me-cHex H R2 Me H COtBu Me H R1 Me H R2 Et H COtBu Et H R1 Et H R2 iPr H COtBu Pr H R1 Pr H R2 nPr H COtBu nPr H R1 nPr H R2 nBu H COtBu nBu H R1 nBu H R2 nPen H COtBu nPen H R1 nPen H R2 nHex H COtBu nHex H R1 nHex H R2 CF₁ H COtBu CF₂ H R1 CF₃ H R2 F H COtBu F H R1 F H R2 F Cl COtBu Cl H COtBu Cl H R1 Cl H R2 Cl H COtBu Cl Cl COtBu OMe H COtBu OiPr H COtBu OtBu H COtBu OPh H COtBu OCF₃ H COtBu 2-pyridyl H COtBu 2-pyridyl H R1 2-pyridyl H R2 3-pyridyl H COtBu 3-pyridyl H R1 3-pyridyl H R2 4-pyridyl H COtBu 4-pyridyl H R1 4-pyridyl H R2 2-thienyl H COtBu 2-thienyl H R1 2-thienyl H R2 2-Me—Ph Me COtBu 2,6-F₂—Ph Me COtBu 2-F-6-CF₁—Ph Me COtBu 2-F-6-Me—Ph Me COtBu 2-Cl-6-F—Ph Me COtBu tBu Me COtBu 2-Me—Ph Et COtBu 2,6-F₂—Ph Et COtBu 2-F-6-CF₄—Ph Et COtBu 2-F-6-Me—Ph Et COtBu 2-Cl-6-F—Ph Et COtBu tBu Et COtBu 2-Me—Ph iPr COtBu 2,6-F₂—Ph iPr COtBu 2-F-6-CF₃—Ph iPr COtBu 2-F-6-Me—Ph iPr COtBu 2-Cl-6-F—Ph iPr COtBu tBu iPr COtBu 2-Me—Ph Ph COtBu 2,6-F₂—Ph Ph COtBu 2-F-6-CF₃—Ph Ph COtBu 2-F-6-Me—Ph Ph COtBu 2-Cl-6-F—Ph Ph COtBu tBu Ph COtBu 2-Me—Ph CF₃ COtBu 2,6-F₂—Ph CF₃ COtBu 2-F-6-CF₃—Ph CF₃ COtBu 2-F-6-Me—Ph CF₃ COtBu 2-Cl-6-F—Ph CF₃ COtBu tBu CF₃ COtBu 2-Me—Ph cPr COtBu 2,6-F₂—Ph cPr COtBu 2-F-6-CF₁—Ph cPr COtBu 2-F-6-Me—Ph cPr COtBu 2-Cl-6-F—Ph cPr COtBu tBu cPr COtBu 2-Me—Ph cHex COtBu 2,6-F₂—Ph cHex COtBu 2-F-6-CF₃—Ph cHex COtBu 2-F-6-Me—Ph cHex COtBu 2-Cl-6-F—Ph cHex COtBu tBu cHex COtBu 2-Me—Ph F COtBu 2,6-F₂—Ph F COtBu 2-F-6-CF₃—Ph F COtBu 2-F-6-Me—Ph F COtBu 2-Cl-6-F—Ph F COtBu tBu F COtBu 2-Me—Ph Cl COtBu 2,6-F₂—Ph Cl COtBu 2-F-6-CF₃—Ph Cl COtBu 2-F-6-Me—Ph Cl COtBu 2-Cl-6-F—Ph Cl COtBu tBu Cl COtBu 2-Me—Ph CO₂Me COtBu 2,6-F₂—Ph CO₂Me COtBu 2-F-6-CF₃—Ph CO₂Me COtBu 2-F-6-Me—Ph CO₂Me COtBu 2-Cl-6-F—Ph CO₂Me COtBu tBu CO₂Me COtBu 2-Me—Ph CO₃Et COtBu 2,6-F₂—Ph CO₃Et COtBu 2-F-6-CF₃—Ph CO₃Et COtBu 2-F-6-Me—Ph CO₃Et COtBu 2-Cl-6-F—Ph CO₃Et COtBu tBu CO₃Et COtBu 2-Me—Ph CO₃tBu COtBu 2,6-F₂—Ph CO₃tBu COtBu 2-F-6-CF₃—Ph CO₃tBu COtBu 2-F-6-Me—Ph CO₃tBu COtBu 2-Cl-6-F—Ph CO₃tBu COtBu tBu CO₃tBu COtBu

(Insecticides and Acaricides)

Compositions containing the compounds of the present invention obtained in such ways as those mentioned above are useful, for example, as agricultural and horticultural insecticides, acaricides, sanitary insect pest controlling agents and anti-fouling agents for aqueous adhesive organisms. It is particularly preferable to apply compositions containing the compounds of the present invention as agricultural and horticultural insecticides and acaricides.

The compounds of the present invention can be used in the pure form without adding other ingredients, when they are actually applied as agricultural and horticultural insecticides or acaricides. When applied as agrochemicals, they may be used in forms that general agrochemicals can take, such as wettable powders, granules, dusts, emulsifiable concentrates, water soluble powders, flowable concentrates and flowables.

In order to make solid formulations, vegetable powders such as soybean flour and wheat flour; fine mineral powders such as diatomaceous earth, apatite, gypsum, talc, bentonite, pyrophylite and clay; and organic and inorganic compounds such as sodium benzoate, urea and Glauber's salt can be used as additives and carriers. When the purpose is to prepare liquid formulations, as additives and carriers, petroleum fractions such as kerosene, xylene and solvent naphtha, cyclohexane, cyclohexanone, DMF, DMSO, alcohol, acetone, trichloroethylene, methyl isobutyl ketone, mineral oils, vegetable oils, water and the like can be used as solvents.

It is possible to further add surfactant, if required, to make these formulations homogeneous and stable forms. There are no particular restrictions on surfactant used. Their examples include nonionic surfactant such as polyoxyethylene-added alkylphenyl ethers, polyoxyethylene-added alkyl ethers, polyoxyethylene-added higher fatty acid esters, polyoxyethylene-added sorbitan higher fatty acid esters and polyoxyethylene-added tristylylphenyl ethers; polyoxyethylene-added alkylphenyl ether sulfates, alkylbenzenesulfonates, higher alcohol sulfates, alkylnaphthalene sulfonates, polycarboxylic acid salts, lignin sulfonates, condensation products of alkylnaphthalene sulfonates with formaldehyde, and copolymers of isobutylene and maleic anhydride.

An amount of the active ingredient (a compound of the present invention) in a formulation is preferably 0.01 to 90% by weight, more preferably about 0.05 to 85% by weight. The obtained wettable powders, emulsifiable concentrates, flowable concentrates and flowables are diluted with water to specified concentrations to use as suspensions or emulsions. The dusts and granules are used as they are to directly spray on plants or soil.

It goes without saying that the compounds of the present invention are sufficiently effective by themselves. They can be used, however, by mixing with one or more of various fungicides, insecticides, acaricides or synergists.

Representative examples of fungicides, insecticides, acaricides and plant growth regulators that can be used to mix with the compounds of the present invention are shown in the following:

Fungicides

Captan, Forpet, Thiuram, Ziram, Zineb, Maneb, Mancozeb, Propineb, Polycarbamate, Chlorotalonyl, Quintozene, Captafol, Iprodione, Prothimidon, Vinclosolin, Fluorimide, Cymoxanil, Mepronyl, Flutoranyl, Penthichlon, Oxycarboxin, Phosethyl-aluminum, Propamocarb, Triazimefon, Triazimenol, Propiconazole, Dichloptrazole, Bitertanol, Hexaconazole, Microbutanil, Flusilazole, Ethaconazole, Fluotrimazole, Flutriafen, Penconazole, Diniconazole, Cyproconazole, Phenalimol, Triflumizole, Prochloraz, Imazaryl, Pefurazoate, Tridemorph, Fenpropymorph, Triforin, Buthiobate, Pryfenox, Anilazine, Polyoxin, Metharaxyl, Oxadixyl, Flaraxyl, Isoprothiorane, Probenazole, Pyrolnitrin, Blasticidin S, Kasugamycin, Validamycin, Sulfric acid dihydrostreptomycin, Benomil, Carbendazim, Thiophanate-methyl, Hymexazole, Basic copper chloride, Basic copper sulfate, Triphenyl tin acetate, Triphenyl tin hydroxide, Diethofencarb, Methasulfocarb, Quinomethionate, Binapacryl, Lecithin, Sodium carbonate, Dithianon, Dinocap, Phenaminosulf, Dichlomezine, Guazatine, Dozin, IBP, Edifenphos, Mepanipyrim, Ferimzone, Trichlamide, Methasulfocarb, Fluazinam, Etokinorakku (oxolinic acid), Dimethomorph, Pyroquiron, Tecrofutaram, Futharide, Phenazinoxyde, Thiabendazole, Tricyclazole, Vinclozolin, Cymoxanil, Cyclobutanyl, Guazatine, Propamocarb-hydrochloride, Oxolinic acid and the like.

Insecticides and Acaricides

Organophosphorus and Carbamate Insecticides

Fenthion, Fenitrothion, Diazinon, Chlorpyrifos, ESP, Vamidothion, Fenthoate, Dimethoate, Formothion, Malathon, Trichlorfon, Thiomethon, Phosmet, Dichlorvos, Acephate, EPBP, Methylparathion, Oxydimethonmethyl, Ethion, Salithion, Cyanophos, Isoxathion, Pyridafenthion, Phosalon, Methidathion, Sulprofos, Chlorfenvinphos, Tetrachlorvinphos, Dimethylvinphos, Propaphos, isofenphos, Ethylthiomethon, Profenofos, Pyrachlofos, Monoclotophos, Adinphosmethyl, Aldicarb, Methomyl, Thiodicarb, Carbofuran, Carbosulfan, Benfuracarb, Furathiocarb, Propoxur, BPMC, MTMC, MIPC, Carbaryl, Pyrimicarb, Ethiofencarb, Fenoxycarb and the like.

Pyrethroid Type Insecticides

Permethrin, Cypermethrin, Deltamethrin, Fenvalerate, Fenpropathrin, Pyrethrin, Allethrin, Tetramethrin, Resmethrin, Dimethrin, Propathrin, Phenothrin, Prothrin, Fulvalinate, Cyfluthrin, Cyhalothrin, Flucythrinate, Ethofenprox, Cycloprothrin, Tralomethrin, Silafluofen, Profenprox, Acrynathrin and the like.

Benzoyl Urea and other Insecticides

Diflubenzuron, Chlorfluazuron, Hexaflumron, Triflumron, Tetrabenzuron, Flufenoxuron, Flucycloxuron, Buprofezin, Pyriproxyfen, Methoprene, Benzoepin (endosulfan), Diafenthiuron, Acetamiprid, Imidacloprid, Nitenpyram, Fipronyl, Caltop, Thiocyclam, Bensultap, Chlorphenapyr, Emanectin-benzoate, Tebufenozide, Nicotine sulfate, Rotenone, Metaldehyde, machine oils, BT, agrochemicals for microbial organisms such as insect disease viruses, and the like.

Nematicides

Phenamiphos, Fosthiazate and the like.

Acaricides

Chlorbenzylate, Phenisobromolate, Dicofol, Amitraz, BPPS, Benzomate, Hexythiazox, Fenbutatin oxide, Polynactins, Quinomethionate, CPCBS, Tetradifon, Abermectin, Milbemectin, Clofentezin, Cyhexatin, Pyridaben, Fenpyroximate, Tebufenpyrad, Pyrimidifen, Phenothiocarb, Dienochlor, Etoxazole, Halfenprox and the like.

Plant Growth Regulators

Gibberellins (for example, gibberellin A3, gibberellin A4 and gibberellin A7), IAA, NAA and the like.

The compound of the present invention can be used to control agricultural pests, sanitary insect pests, stored grain insect pests, cloth insect pests, house insect pests and the like, and have activities of killing adults, nymphs, larvae and eggs. Their representative examples are shown in the following:

Examples of Lepidopterous pest insects include cotton leafworm, cabbage armyworm, black cutworm, common cabbegeworm, cabbage looper, diamond-back, smaller tea tortrix, tea leaf roller, peach fruit moth, oriental fruit moth, citrus leaf miner, tea leaf roller, apple leaf miner, gypsy moth, tea tussock moth, rice stem borer, grass leaf roller, European corn borer, fall webworm, almond moth, Heliothis sp., Helicoverpa sp., Agrotis sp., casemaking clothes moth, codling moth and cotton bollworm.

Examples of Hemipterous pest insects include green peach aphid, cotton aphid, turnip aphid, grain aphid, bean bug, common green stink bug, arrowhead scale, mulberry mealy scale, greenhouse whitefly, tabacco whitefly, pear psylla, Japanese pear lace bug, brown planthopper, small brown planthopper, white-backed planthopper and green rice leafhopper.

Examples of Coleopterous pest insects include striped flea beetle, cucurbit leaf beetle, Colorado potato beetle, rice water weevil, rice weevil, adzuki bean weevil, Japanese beetle, soybean beetle, Diabrotica sp., cigarette beetle, powder post beetle, pine sawyer, white-spotted longicorn beetle, Agriotis sp., 28-spotted ladybeetle, rust-red flour beetle and cotton boll weevil.

Examples of Dipterous pest insects include housefly, Calliphora lata, Boettcherisca peregrina, cucurbit fruit fly, citrus fruit fly, seed maggot, rice leaf miner, yellow drosophila, Stomoxys calcitrans, Culex tritaeniarhynchus, Aedes aegypti and Anlopheles hyrcanus.

Examples of Thysanopterous pest insects include Thrips palmi and tea thrips.

Examples of Hymenopterous pest insects include Monomorium pharaonis, yellow harnet and cabbage sawfly.

Examples of Orthopterous pest insects include grasshopper.

Examples of Dictyopterous pest insects include German cockroach, American cockroach and Japanese cockroach.

Examples of Isopterous pest insects include Formosan subterranean termite and Reticulitermes speratus Kolbe.

Examples of Aphanipterous pest insects include human flea.

Examples of Anoplurous pest insects include human louse.

Examples of mites include two-spotted spider mite, Kanzawa spider mite, citrus red mite, European red mite, citrus rust mite, apple rust mite, Tarsonemus sp., Brevipalpus sp., Eotetranychus sp., Robin bulb mite, common grain mite, Desmatophagoides farinae, Boophilus microplus and Haemaphysallis bispinosa.

Examples of plant-parasitic nematodes include southern root-knot nematode, root lesion nematode, soybean cyst nematode, rice white-tip nematode and pine wood nematode.

Many pests such as diamond-back, planthoppers, leafhoppers and aphids, and phytophagous mites have developed resistance against organophosphorus pesticides, carbamate insecticides and acaricides. Therefore, the chemicals have had the problem of lack of efficacy. There has been a desire for chemicals effective on pests and mites of resistant strains. The compounds of the present invention are chemicals having excellent insecticidal and acaricidal effects on pests resistant to organophosphorus pesticides, carbamate insecticides or pyrethroid type agents and mites resistant to acaricides, as well as those of sensitive strains.

The compounds of the present invention induce very slight chemical injuries, have low toxicity on fish and warm-blood animals, and are highly safe.

BEST FORMS TO IMPLEMENT THE INVENTION

The present invention is further described in detail in reference to a Reference Example and Examples.

Reference Example 1 Preparation of 2-[4-(2,6-difluorophenyl)-2-thiazolyl]-3-hydroxy-2′-trifluoromethy-cinnamonitrile

To a solution of 0.8 g (4.2 mmol) of 2-trifluoromethylbenzoic acid in 10 ml of THF was added 0.69 g (4.2 mmol) of carbonylbisimidazole, followed by stirring at room temperature for an hour. To the mixture was added 1.0 g(4.2 mmol) of 2-cyanomethyl-4-(2,6-difluorophenyl)thiazole, and then, 0.17 g (4.2 mmol) of sodium hydride (60% in oil) in an ice-bath. After stirring at room temperature for an hour, another equivalent of sodium hydride (0.17 g, 4.2 mmol: 60% in oil) was added, followed by stirring at room temperature overnight. The reaction mixture was poured into ice-water, acidified with dilute hydrochloric acid, and then, extracted with ethyl acetate. The organic layer was concentrated under diminished pressure, followed by chromatography on silica-gel column (ethyl acetate/n-hexane=1/1, as an eluent) to give 1.1 g(64%) of the title compound. Melting point: 170-172° C.

EXAMPLE 1

Preparation of 2-[4-(2,6-difluorophenyl)-2-thiazolyl]-3-pivaloyloxy-2′-trifluormethyl-cinnamonitrile (Compound No. 3-1)

To a solution of 0.6 g (1.5 mmol) of 2-[4-(2,6-difluorophenyl)-2-thiazolyl]-3-hydroxy-2′-trifluoromethylcinnamonitrile in 5 ml of THF were added 0.16 g (1.6 mmol) of triethylamine and 0.2 g (1.6 mmol) of pivaloyl chloride in an ice-bath, respectively, and then, the mixture was stirred at room temperature for 2 hours. After the precipitate was filtered, the filtrate was concentrated under diminished pressure, followed by chromatography on silica-gel column (ethyl acetate/n-hexane=1/4, as an eluent) to give 0.28 g (39%). Melting point: 163-165° C.

Representative examples of the compounds of the present invention that were prepared in such ways as described above are shown in Table 5. The NMR data of oily substances and others are in Table 6.

The symbols used in the tables have the same meanings as those for Tables 1 to 4.

TABLE 5

Compound Physical No. A B R Xn constant* 5-1 2,6-F₂—Ph H COtBu 2-CF₃   [163-165] a 5-2 2,6-F₂—Ph H COMe 2-CF₃   [165-167] a 5-3 2,6-F₂—Ph H COPh 2-CF₃ [135-136] 5-4 2,6-F₂—Ph H COtBu 2-Me [111-121] 5-5 2,6-F₂—Ph H COMe 2-Me [120-128] 5-6 2,6-F₂—Ph H COPh 2-Me    [182-183.5] a 5-7 2,6-F₂—Ph H R35 2-Me Viscous oil 5-8 2,6-F₂—Ph H COtBu 2-Cl [143-146] 5-9 2,6-F₂—Ph H COtBu 2,6-F   [141-143.5] 5-10 2,6-F₂—Ph H COtBu 2-Cl-6-F n_(D) ^(20.4) 1.5726 5-11 2,6-F₂—Ph H COtBu 2-F-6-CF₃ Viscous oil 5-12 2,6-F₂—Ph H COtBu 2-Br [119-122] 5-13 2,6-F₂—Ph H COtBu 2-OMe [72-74] 5-14 2,6-F₂—Ph H COtBu 2,3-F₂—6-CF₃ [142-144] 5-15 2-F—Ph H COtBu 2-CF₃ Viscous oil 5-16 3-F—Ph H COtBu 2-CF₃ Viscous oil 5-17 4-F—Ph H COtBu 2-CF₃ Viscous oil 5-18 2-Cl—Ph H COtBu 2-CF₃ Viscous oil 5-19 3-Cl—Ph H COtBu 2-CF₃ Viscous oil 5-20 tBu H COtBu 2-CF₃ n_(D) ^(20.9) 1.5193 5-21 tBu H COtBu 2,6-F₂ Viscous oil 5-22 tBu H COtBu 2,3-F₂-6-CF₃ [181-183] 5-23 cHex H R34 2-Me   [128-129.5] 5-24 2,6-F₂—Ph H COcPr 2-Me [146-148] 5-25 2,6-F₂—Ph H COiPr 2-Me [137-139] 5-26 2,6-F₂—Ph H R1 2-Me [120-122] 5-27 2,6-F₂—Ph H CO₂nPr 2-Me Viscous oil 5-28 2,6-F₂—Ph H CO₂CH₂Ph 2-Me Viscous oil 5-29 2,6-F₂—Ph H SO₂nPr 2-CF₃ [115-119] 5-30 2,6-F₂—Ph H SO₂Me 2-Me [163-165] 5-31 2,6-F₂—Ph H SO₂nPr 2-Me Viscous oil 5-32 2,6-F₂—Ph H COtBu 2-Et [98.5-99.5] 5-33 2,6-F₂—Ph H COtBu 2-F [153-155] 5-34 2,6-F₂—Ph H COtBu 2-NO₂ Viscous oil 5-35 2,6-F₂—Ph H COtBu 2-OCF₃ [114-117] 5-36 2,6-F₂—Ph H COtBu 2-CO₂Et [127-130] 5-37 2,6-F₂—Ph H COtBu 2,6-Cl₂ [154-159] 5-38 2,6-F₂—Ph H COtBu 2-Me-3-F [131-135] 5-39 2,6-F₂—Ph H COtBu 2-Me-4-F [131-143] 5-40 2,6-F₂—Ph H COtBu 2-Me-5-F [108-109] 5-41 2,6-F₂—Ph H COtBu 2-Me-6-F [103-104] 5-42 2,6-F₂—Ph Me COtBu 2-Me [140-141] 5-43 2,6-F₂—Ph Me COMe 2-Me Viscous oil 5-44 2-Cl—Ph H COtBu 2-Me [123-125] 5-45 2-Cl—Ph H COtBu 2-Cl [106-107] 5-46 2-Cl—Ph H COtBu 2,6-F₂ [144-147] 5-47 4-Cl—Ph H COtBu 2-CF₃ Viscous oil 5-48 2-CF₃—Ph H COtBu 2-CF₃ [146-147] 5-49 2-CF₃—Ph H COtBu 2-Me [131-132] 5-50 2-CF₃—Ph H COtBu 2,6-F₂ [86-87] 5-51 2-CF₃—Ph H COtBu 2-Cl [140-141] 5-52 2-F—Ph H COtBu 2-Me [144-145] 5-53 2-F—Ph H COMe 2-Me [127-129] 5-54 2-F—Ph H COPh 2-Me [140-143] 5-55 2-F—Ph H COtBu 2-Cl [143-145] 5-56 3-F—Ph H COtBu 2-Me [129-130] 5-57 3-F—Ph H COMe 2-Me [119-120] 5-58 3-F—Ph H COPh 2-Me [148-149] 5-59 3-F—Ph H COtBu 2-Cl [150-151] 5-60 2-Me—Ph H COtBu 2-CF₃ Viscous oil 5-61 2-Me—Ph H R31 2-Me [161-164] 5-62 2-Me—Ph H COtBu 2-Me [118-119] 5-63 2-Me—Ph H COtBu 2-F [123-125] 5-64 2-Me—Ph H COtBu 2-Cl n_(D) ^(20.2) 1.5808 5-65 2-Me—Ph H COtBu 2-Br  [99-103] 5-66 2-Me—Ph H COtBu 2,6-F₂ [133-135] 5-67 2-Me—Ph H COtBu 2-Cl-6-F [124-126] 5-68 2-Me—Ph H COtBu 2-Me-6-F [125-129] 5-69 3-Me—Ph H COtBu 2-CF₃ Viscous oil 5-70 3-Me—Ph H R31 2-Me [130—131] 5-71 3-Me—Ph H COtBu 2-Me Viscous oil 5-72 3-Me—Ph H COtBu 2,6-F₂ [103-105] 5-73 2,3-F₂—Ph H COtBu 2-CF₃ [134-136] 5-74 2,3-F₂—Ph H COtBu 2-Me [101-102] 5-75 2,5-F₂—Ph H COtBu 2-CF₃ [134-136] 5-76 2,5-F₂—Ph H COtBu 2-Me [126-128] 5-77 3,5-F₂—Ph H COtBu 2-Me [114-116] 5-78 2,3,6-F₂—Ph H COtBu 2-Me [105-107] 5-79 2-Cl-6-F—Ph H COtBu 2-CF₃ [150-163] 5-80 2-Cl-6-F—Ph H COtBu 2-Me [121-122] 5-81 2-Cl-6-F—Ph H COtBu 2-Cl [123-126] 5-82 2-Cl-6-F—Ph H COtBu 2,6-F₂ [136-138] 5-83 2-Me-3-F—Ph H COtBu 2-Me  [99-104] 5-84 2-Me-4-F—Ph H COtBu 2-Me [139-144] 5-85 2-Me-5-F—Ph H COtBu 2-Me [146-149] 5-86 2-Me-5-F—Ph H COtBu 2-Me   [111-116] b 5-87 2-Me-6-F—Ph H COtBu 2-CF₃  [98-101] 5-88 2-Me-6-F—Ph H COtBu 2-Me [109-111] 5-89 2-OMe-5-F—Ph H COtBu 2-Me [148-153] 5-90 2-OMe-5-Cl—Ph H COtBu 2-Me [144-156] 5-91 2-OMe-3,5-F₂—Ph H COtBu 2-Me [134-136] 5-92 4-OCF₃—Ph H COtBu 2-CF₃ Viscous oil 5-93 4-OCF₃—Ph H COtBu 2-Me [123-124] 5-94 4-OCF₃—Ph H COtBu 2-Cl [119-120] 5-95 Me H COtBu 2-Me Viscous oil 5-96 tBu H COtBu 2-Me [112-113] 5-97 tBu H COMe 2-Me n_(D) ^(21.5) 1.5800 5-98 tBu H R31 2-Me [125-126] 5-99 2-pyridyl H COtBu 2-Me [153-157] 5-100 2-thienyl H COtBu 2-Me [134-138] 5-101 2,6-F₂—Ph H COtBu 2-Cl-4-F [155-157] 5-102 2,6-F₂—Ph H COtBu 2-F-6-OMe [153-155] 5-103 1-Me-cHex H COtBu 2-Me [96-98] 5-104 1-Me-cHex H COtBu 2-CF₃ [92-93] 5-105 2-Me-cHex H COtBu 2-Me [92-94] 5-106 2-Me-cHex H COtBu 2-CF₃ [82-85] 5-107 2,6-F₂—Ph H R2 2-Me [96-98] 5-108 2,6-F₂—Ph H R1 2-CF₃ [156-158] 5-109 2,6-F₂—Ph H R2 2-CF₃ [101-103] 5-110 cHex H COtBu 2-Me Viscous oil *[ ]: Melting point ° C., and n_(D): refractive index. These are the same for the following tables. a: One of isomers. Others are a mixture of isomers. b: Isomer of Compound No. 5-85.

TABLE 6 NMR Data Compound No ¹H—NMR (CDCl₃, δppm) 5-7 1.68 and 1.70(total 6H, 2s), 2.06 and 2.30 (total 3H, 2s), 6.90-7.05(2H, m), 7.10-7.49(m) and 7.59(s) (total 10H) 5-11 1.27 and 1.33(total 9H, 2s), 6.83-7.08(2H, m), 7.20-7.70(m) and 7.76(s) (total 5H) 5-15 1.29 and 1.32(total 9H, 2s), 6.95-7.12(1H, m), 7.29-7.51(2H, m), 7.63-7.90(6H, m) 5-16 1.29 and 1.32(total 9H, 2s), 7.03-7.40(3H, m), 7.62-8.00(m) and 8.33-8.41(m) (total 6H) 5-17 1.28 and 1.30(total 9H, 2s), 7.00-7.19(2H, m), 7.60(1H, s), 7.61-7.90(4H, m), 7.93-8.00(2H, m) 5-18 1.29 and 1.30(total 9H, 2s), 7.25-7.51(4H, m), 7.61-7.90(4H, m), 8.09 and 8.12(total 1H, 2s) 5-19 1.28 and 1.31(total 9H, 2s), 7.30-7.41(2H, m), 7.62-7.90(6H, m), 7.97(1H, bs) 5-21 1.10, 1.32, 1.33 and 1.36(total 18H, 4s), 6.89- 7.12(total 3H, m), 7.39-7.54(1H, m) 5-27 1.92 and 1.96(total 3H, 2s), 1.61-1.79(2H, m), 2.34 and 2.53(total 3H, 2s), 4.17 and 4.18(total 2H, 2t), 6.91-7.00(2H, m), 7.28-7.72(6H, m) 5-28 2.48 and 2.49(total 3H, 2s), 5.19 and 5.21(total 2H, 2s), 6.92-7.70(13H, m) 5-31 1.96(3H, t), 1.81-1.98(2H, m), 2.53(3H, s), 2.99 (2H, dd), 6.97-7.08(2H, m), 7.28-7.62(5H, m), 7.76(1H, bs) 5-34 1.23 and 1.29(total 9H, 2s), 6.90 and 7.01(total total 2H, 2t), 7.20-7.40(1H, m), 7.51-7.95(4H, m), 8.20-8.28(1H, m) 5-43 2.19, 2.28, 2.33, 2.35, 2.44 and 2.50(total 9H, 6s), 6.92-7.12(2H, m), 7.27-7.58(5H, m) 5-47 1.30 and 1.34(total 9H, 2s), 7.15-7.46 and 7.59- 7.96(total 9H, 2m) 5-60 1.29 and 1.32(total 9H, 2s), 2.32 and 2.50(total 3H, 2s), 7.15-7.33(4H, m), 7.48-7.91(5H, m) 5-69 1.30 and 1.33(total 9H, 2s), 2.37 and 2.42(total 3H, 2s), 7.18-7.38(2H, m), 7.63-7.90(7H, m) 5-71 1.32 and 1.33(total 9H, 2s), 2.31, 2.39, 2.42 and 2.59(total 6H, 4s), 7.12-7.87(9H, m) 5-92 1.30 and 1.33(9H, 2s), 7.14-7.40, 7.66-7.90 and 7.98-8.04(total 9H, 3m) 5-95 1.32(9H, s), 2.52(3H, s), 2.56(3H, s), 7.04(1H, bs), 7.23-7.48(4H, m) 5-110 1.20-1.57(5H, m), 1.35(9H, s), 1.73-1.91(3H, m), 2.11-2.20(2H, m), 2.59(3H, s), 2.82-2.95 (1H, m), 7.03(1H, s), 7.28-7.50(4H, m)

A few examples of compositions of the present invention are described below. Additives and addition ratios are not limited to those in the examples, and can be changed in a wide range. The “parts” used in the formulation examples are parts by weight.

EXAMPLE 2

Wettable Powder

A compound of the present invention 40 parts Diatomaceous earth 53 parts Higher alcohol sulfate 4 parts Alkylnaphthalene sulfonate 3 parts

The above compounds were mixed uniformly and pulverized finely to give a wettable powder containing 40% of the active ingredient.

EXAMPLE 3

Emulsifiable Concentrate

A compound of the present invention 30 parts Xylene 33 parts Dimethylformamide 30 parts Polyoxyethylene alkylallyl ether 7 parts

The above compounds were mixed and solved to give an emulsifiable concentrate containing 30% of the active ingredient.

EXAMPLE 4

Dust

A compound of the present invention 10 parts Talc 89 parts Polyoxyethylene alkylallyl ether 1 part

The above compounds were mixed uniformly and pulverized finely to give a dust containing 10% of the active ingredient.

EXAMPLE 5

Granules

A compound of the present invention 5 parts Clay 73 parts Bentonite 20 parts Sodium dioctylsulfosuccinate 1 part Sodium phosphate 1 part

The above compounds were sufficiently pulverized and mixed. Water was added to it to knead well, followed by granulation and drying to give granules containing 5% of the active ingredient.

EXAMPLE 6

Flowable Concentrate

A compound of the present invention 10 parts Sodium lignin sulfonate 4 parts Sodium dodecylbenzenesulfonate 1 part Xanthane gum 0.2 parts Water 84.8 parts

The above compounds were mixed and wet pulverized until the granule size became smaller than 1 μ, to give a flowable concentrate containing 10% of the active ingredient.

Availability in Industry

Examples are shown below that formulations containing compounds of the present invention, which were prepared according to such ways as described above, were applied as agricultural and horticultural insecticides and acaricides.

Test Example 1

Effects on Pseudaletia separata Walker

According to the instructions of the wettable powder described in the above Example 2, a wettable powder was diluted with water to make the compound concentration 125 ppm. Corn leaves were immersed in the solution for 30 seconds, air-dried and placed in a Petri dish containing 5 third instar larvae of Pseudaletia separata Walker. The dish was covered with a glass lid and placed in a thermostatic chamber of temperature of 25° C. and relative humidity of 65%. Mortality was assessed 6 days after treatment. Each test was replicated twice.

The results show that the following compounds had mortality of 100%.

5-1, 5-2, 5-3, 5-4, 5-5, 5-6, 5-7, 5-8, 5-9, 5-10, 5-11, 5-12, 5-13, 5-15, 5-16, 5-17, 5-18, 5-20, 5-21, 5-22, 5-23, 5-24, 5-25, 5-26, 5-27, 5-28, 5-30, 5-31, 5-33, 5-34, 5-38, 5-39, 5-40, 5-41, 5-48, 5-49, 5-50, 5-51, 5-54, 5-56, 5-57, 5-58, 5-59, 5-60, 5-61, 5-62, 5-63, 5-64, 5-65, 5-66, 5-67, 5-68, 5-69, 5-74, 5-78, 5-80, 5-83, 5-84, 5-85, 5-86, 5-87, 5-88, 5-96, 5-97, 5-99, 5-100, 5-101, 5-102, 5-103, 5-104, 5-105, 5-106, 5-107, 5-108, 5-109 and 5-110.

Chlordimeform used as a control killed 40% of the larvae.

Test Example 2

Effects on Aphis gossypii Glover

Adults of Aphis gossypii Glover were inoculated on cucumber seedlings planted in a 10-cm (diameter) pot and 10 days old after the germination. On the following day the adult aphids were removed, According to the instructions of the emulsifiable concentrate described in the above Example 3, an emulsifiable concentrate was diluted with water to make a compound concentration 8 ppm. The diluted formulation was sprayed over the cucumber seedlings infested with hatched nymphs. The seedlings were placed in a thermostatic chamber of temperature of 25° C. and relative humidity of 65%. Mortality was assessed 6 days after treatment. Each test was replicated twice.

The results show that the following compounds had mortality of 100 %.

5-1, 5-3, 5-4, 5-5, 5-6, 5-7, 5-8, 5-10, 5-12, 5-13, 5-15, 5-16, 5-20, 5-24, 5-25, 5-26, 5-27, 5-28, 5-30, 5-31, 5-33, 5-38, 5-39, 5-40, 5-41, 5-44, 5-45, 5-49, 5-51, 5-52, 5-54, 5-55, 5-56, 5-57,5-58, 5-60, 5-61, 5-62, 5-63, 5-64, 5-65, 5-68, 5-69, 5-71, 5-74, 5-76, 5-77, 5-78, 5-79, 5-80, 5-83, 5-84, 5-85, 5-86, 5-87, 5-88, 5-89, 5-90, 5-91, 5-96, 5-99, 5-100, 5-101, 5-102, 5-103, 5-104, 5-105, 5-106, 5-107, 5-108, 5-109 and 5-110.

The known compounds shown in the following and used as controls killed none of the nymphs.

Control Compound A

A compound disclosed in Japanese Patent Laid-open No. Sho 53-92769

Control Compound B

A compound disclosed in Japanese Patent Laid-open No. Sho 55-154963

Control Compound C

A compound disclosed in EP 189960

Control Compound D

A compound disclosed in Japanese Patent Laid-open No. Sho 55-154962

Control Compound E

A compound disclosed in Japanese Patent Laid-open No. Hei 10-298169 and WO 95/29591 

What is claimed is:
 1. A compound represented by the formula (1)

wherein A is C₁₋₆ alkyl, C₃₋₆ cycloalkyl optionally substituted by halogen, C₁₋₆ alkyl, C₁₋₆ alkoxy or nitro, pyridyl optionally substituted by halogen, C₁₋₆ alkyl, C₁₋₆ alkoxy or nitro, thienyl optionally substituted by halogen, C₁₋₆ alkyl, C₁₋₆ alkoxy or nitro, or 2,6 di-substituted phenyl by halogen, C₁₋₆ alkyl, C₁₋₆ alkoxy or nitro; B is hydrogen; R is a group of Formula COR¹ (wherein R¹ is C₁₋₁₂ alkyl, C₁₋₆ haloalkyl, optionally substituted C₃₋₆ cycloalkyl, C₁₋₆ alkoxy, C₁₋₆ alkoxy C₁₋₆ alkyl, C₁₋₆ alkylthio C₁₋₆ alkyl, mono-C₁₋₆ alkylamino, di-C₁₋₆ alkylamino, optionally substituted phenyl C₁₋₆ alkyl, optionally substituted phenoxy C₁₋₆ alkyl, optionally substituted phenylthio C₁₋₆ alkyl or optionally substituted phenyl, or a group of Formula SO₂R² (wherein R² is C₁₋₆ alkyl or optionally substituted phenyl); X is halogen, C₁₋₆ alkyl, C₁₋₆ haloalkyl, or C₁₋₆ alkoxy and at least one of the substituents is at position 2; and n is an integer between 1 and
 5. 2. A pest controlling agent containing one or more compounds of Formula (1)

(wherein A, B, R, X and n are as defined above) as active ingredients. 